Nová doporučení pro srdeční resynchronizační léčbu

Prezentace na téma: "Nová doporučení pro srdeční resynchronizační léčbu"— Transkript prezentace:

1 Nová doporučení pro srdeční resynchronizační léčbu
M. Táborský XX. výroční sjezd ČKS Brno

2 Evropská doporučení pro diagnostiku a léčbu srdečního selhání

3 Cardiac Resynchronization Therapy in HF
CARE HF, Companion, Miracle and Miracle ICD Path CHF I/II, Contak CD Mustic AF and Mustic SR REVERSE, MADIT-CRT RAFT Studies MDT studies in orange NYHA Class Treatment of HF Prevention of HF Objective NYHA IV NYHA III NYHA II NYHA I

4 REVERSE ® Comparison between CRT ON and OFF in mild HF
73 centers: US (37), Europe (35), Canada (1) Enrolment n=610 Randomization Double-blinded Follow-up CRT ON n=419 n=180 NYHA Class II or I (previously symp.) QRS 120 ms LVEF 40% Primary endpoint: HF Clinical Composite Response (worsened) LVESVi 2:1 ON vs OFF Prevention of Disease Progression by Cardiac Resynchronization Therapy in Patients With Asymptomatic or Mildly Symptomatic Left Ventricular Dysfunction Insights From the European Cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) Trial Claude Daubert, Michael R. Gold, William T. Abraham, Stefano Ghio, Christian Hassager, Grahame Goode, Tama´s Szili-Török, Cecilia Linde, on behalf of the REVERSE Study Group Objectives The aim of this study was to determine the long-term effects of cardiac resynchronization therapy (CRT) in the European cohort of patients enrolled in the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. Background Previous data suggest that CRT slows disease progression and improves the outcomes of asymptomatic or mildly symptomatic patients with left ventricular (LV) dysfunction and a wide QRS complex. Methods We randomly assigned 262 recipients of CRT pacemakers or defibrillators, with QRS 120 ms and LV ejection fraction 40% to active (CRT ON; n 180) versus control (CRT OFF; n 82) treatment, for 24 months. Mean baseline LV ejection fraction was 28.0%. All patients were in sinus rhythm and receiving optimal medical therapy. The primary study end point was the proportion worsened by the heart failure (HF) clinical composite response. The main secondary study end point was left ventricular end-systolic volume index (LVESVi). Results In the CRT ON group, 19% of patients were worsened versus 34% in the CRT OFF group (p 0.01). The LVESVi decreased by a mean of ml/m2 in the CRT ON, versus ml/m2 in the CRT OFF group (p 0.0001). Time to first HF hospital stay or death (hazard ratio: 0.38; p ) was significantly delayed by CRT. Conclusions After 24 months of CRT, and compared with those of control subjects, clinical outcomes and LV function were improved and LV dimensions were decreased in this patient population in New York Heart Association functional classes I or II. These observations suggest that CRT prevents the progression of disease in patients with asymptomatic or mildly symptomatic LV dysfunction. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT ) J Am Coll Cardiol 2009;54: CRT OFF n=191 n=82 12 m. analysis EU and US 24 m. analysis EU only Daubert JC. J Am Coll Cardiol 2009; 54:

5 REVERSE 24 m.: Primary Endpoint
Significantly less pts. worsened over time in the CRT group as measured by the clinical composite response Prevention of Disease Progression by Cardiac Resynchronization Therapy in Patients With Asymptomatic or Mildly Symptomatic Left Ventricular Dysfunction Insights From the European Cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) Trial Claude Daubert, Michael R. Gold, William T. Abraham, Stefano Ghio, Christian Hassager, Grahame Goode, Tama´s Szili-Török, Cecilia Linde, on behalf of the REVERSE Study Group Objectives The aim of this study was to determine the long-term effects of cardiac resynchronization therapy (CRT) in the European cohort of patients enrolled in the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. Background Previous data suggest that CRT slows disease progression and improves the outcomes of asymptomatic or mildly symptomatic patients with left ventricular (LV) dysfunction and a wide QRS complex. Methods We randomly assigned 262 recipients of CRT pacemakers or defibrillators, with QRS 120 ms and LV ejection fraction 40% to active (CRT ON; n 180) versus control (CRT OFF; n 82) treatment, for 24 months. Mean baseline LV ejection fraction was 28.0%. All patients were in sinus rhythm and receiving optimal medical therapy. The primary study end point was the proportion worsened by the heart failure (HF) clinical composite response. The main secondary study end point was left ventricular end-systolic volume index (LVESVi). Results In the CRT ON group, 19% of patients were worsened versus 34% in the CRT OFF group (p 0.01). The LVESVi decreased by a mean of ml/m2 in the CRT ON, versus ml/m2 in the CRT OFF group (p 0.0001). Time to first HF hospital stay or death (hazard ratio: 0.38; p ) was significantly delayed by CRT. Conclusions After 24 months of CRT, and compared with those of control subjects, clinical outcomes and LV function were improved and LV dimensions were decreased in this patient population in New York Heart Association functional classes I or II. These observations suggest that CRT prevents the progression of disease in patients with asymptomatic or mildly symptomatic LV dysfunction. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT ) J Am Coll Cardiol 2009;54: Daubert JC. J Am Coll Cardiol 2009; 54:

6 HF Hospitalization and Mortality
CRT reduced HF hospitalization and mortality % Hospitalized for HF or Dead % Hospitalized for HF % Mortality Prevention of Disease Progression by Cardiac Resynchronization Therapy in Patients With Asymptomatic or Mildly Symptomatic Left Ventricular Dysfunction Insights From the European Cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) Trial Claude Daubert, Michael R. Gold, William T. Abraham, Stefano Ghio, Christian Hassager, Grahame Goode, Tama´s Szili-Török, Cecilia Linde, on behalf of the REVERSE Study Group Objectives The aim of this study was to determine the long-term effects of cardiac resynchronization therapy (CRT) in the European cohort of patients enrolled in the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. Background Previous data suggest that CRT slows disease progression and improves the outcomes of asymptomatic or mildly symptomatic patients with left ventricular (LV) dysfunction and a wide QRS complex. Methods We randomly assigned 262 recipients of CRT pacemakers or defibrillators, with QRS 120 ms and LV ejection fraction 40% to active (CRT ON; n 180) versus control (CRT OFF; n 82) treatment, for 24 months. Mean baseline LV ejection fraction was 28.0%. All patients were in sinus rhythm and receiving optimal medical therapy. The primary study end point was the proportion worsened by the heart failure (HF) clinical composite response. The main secondary study end point was left ventricular end-systolic volume index (LVESVi). Results In the CRT ON group, 19% of patients were worsened versus 34% in the CRT OFF group (p 0.01). The LVESVi decreased by a mean of ml/m2 in the CRT ON, versus ml/m2 in the CRT OFF group (p 0.0001). Time to first HF hospital stay or death (hazard ratio: 0.38; p ) was significantly delayed by CRT. Conclusions After 24 months of CRT, and compared with those of control subjects, clinical outcomes and LV function were improved and LV dimensions were decreased in this patient population in New York Heart Association functional classes I or II. These observations suggest that CRT prevents the progression of disease in patients with asymptomatic or mildly symptomatic LV dysfunction. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT ) J Am Coll Cardiol 2009;54: Daubert JC. J Am Coll Cardiol 2009; 54:

7 1 month after randomization
MADIT-CRT Comparison between ICD and CRT-D in mild HF 110 centers: US (88), Europe (20), Canada (2) Enrolment n=1,820 Randomization Unblinded Follow-up Event -driven 29 months CRT-D n=1089 NYHA II NYHA I (ischaemic) EF ≤30% QRS 130 ms OMT Primary endpoint: Heart failure or death, whichever comes first 3:2 CRT-D vs ICD Cardiac-Resynchronization Therapy for the Prevention of Heart-Failure Events Arthur J. Moss, W. Jackson Hall, David S. Cannom, Helmut Klein, Mary W. Brown, James P. Daubert, N.A. Mark Estes III, Elyse Foster, Henry Greenberg, Steven L. Higgins, Marc A. Pfeffer, Scott D. Solomon, M.D., David Wilber, and Wojciech Zareba, for the MADIT-CRT Trial Investigators Background This trial was designed to determine whether cardiac-resynchronization therapy (CRT) with biventricular pacing would reduce the risk of death or heart-failure events in patients with mild cardiac symptoms, a reduced ejection fraction, and a wide QRS complex. Methods During a 4.5-year period, we enrolled and followed 1820 patients with ischemic or nonischemic cardiomyopathy, an ejection fraction of 30% or less, a QRS duration of 130 msec or more, and New York Heart Association class I or II symptoms. Patients were randomly assigned in a 3:2 ratio to receive CRT plus an implantable cardioverter– defibrillator (ICD) (1089 patients) or an ICD alone (731 patients). The primary end point was death from any cause or a nonfatal heart-failure event (whichever came first). Heartfailure events were diagnosed by physicians who were aware of the treatment assignments, but they were adjudicated by a committee that was unaware of assignments. Results During an average follow-up of 2.4 years, the primary end point occurred in 187 of 1089 patients in the CRT–ICD group (17.2%) and 185 of 731 patients in the ICD-only group (25.3%) (hazard ratio in the CRT–ICD group, 0.66; 95% confidence interval [CI], 0.52 to 0.84; P = 0.001). The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy. The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events, a finding that was evident primarily in a prespecified subgroup of patients with a QRS duration of 150 msec or more. CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction. There was no significant difference between the two groups in the overall risk of death, with a 3% annual mortality rate in each treatment group. Serious adverse events were infrequent in the two groups. Conclusions CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex. (ClinicalTrials.gov number, NCT ) N Engl J Med 2009;361: ICD n=731 Follow up 1 month after randomization Follow up visits every 3 months Moss A. N Engl J Med 2009; 361:

8 CRT reduces HF/Mortality in mild HF
372 primary endpoints occcured during an average follow-up of 2.4 years: 17.2% (CRT-D) vs. 25.3% (ICD) HR (95% CI): 0.66 ( ) Cardiac-Resynchronization Therapy for the Prevention of Heart-Failure Events Arthur J. Moss, W. Jackson Hall, David S. Cannom, Helmut Klein, Mary W. Brown, James P. Daubert, N.A. Mark Estes III, Elyse Foster, Henry Greenberg, Steven L. Higgins, Marc A. Pfeffer, Scott D. Solomon, M.D., David Wilber, and Wojciech Zareba, for the MADIT-CRT Trial Investigators Background This trial was designed to determine whether cardiac-resynchronization therapy (CRT) with biventricular pacing would reduce the risk of death or heart-failure events in patients with mild cardiac symptoms, a reduced ejection fraction, and a wide QRS complex. Methods During a 4.5-year period, we enrolled and followed 1820 patients with ischemic or nonischemic cardiomyopathy, an ejection fraction of 30% or less, a QRS duration of 130 msec or more, and New York Heart Association class I or II symptoms. Patients were randomly assigned in a 3:2 ratio to receive CRT plus an implantable cardioverter– defibrillator (ICD) (1089 patients) or an ICD alone (731 patients). The primary end point was death from any cause or a nonfatal heart-failure event (whichever came first). Heartfailure events were diagnosed by physicians who were aware of the treatment assignments, but they were adjudicated by a committee that was unaware of assignments. Results During an average follow-up of 2.4 years, the primary end point occurred in 187 of 1089 patients in the CRT–ICD group (17.2%) and 185 of 731 patients in the ICD-only group (25.3%) (hazard ratio in the CRT–ICD group, 0.66; 95% confidence interval [CI], 0.52 to 0.84; P = 0.001). The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy. The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events, a finding that was evident primarily in a prespecified subgroup of patients with a QRS duration of 150 msec or more. CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction. There was no significant difference between the two groups in the overall risk of death, with a 3% annual mortality rate in each treatment group. Serious adverse events were infrequent in the two groups. Conclusions CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex. (ClinicalTrials.gov number, NCT ) N Engl J Med 2009; 361: Moss A. N Engl J Med 2009; 361:

9 MADIT-CRT: Echo Results
Similar improvements in LV function were seen with CRT-D as in REVERSE Cardiac-Resynchronization Therapy for the Prevention of Heart-Failure Events Arthur J. Moss, W. Jackson Hall, David S. Cannom, Helmut Klein, Mary W. Brown, James P. Daubert, N.A. Mark Estes III, Elyse Foster, Henry Greenberg, Steven L. Higgins, Marc A. Pfeffer, Scott D. Solomon, M.D., David Wilber, and Wojciech Zareba, for the MADIT-CRT Trial Investigators Background This trial was designed to determine whether cardiac-resynchronization therapy (CRT) with biventricular pacing would reduce the risk of death or heart-failure events in patients with mild cardiac symptoms, a reduced ejection fraction, and a wide QRS complex. Methods During a 4.5-year period, we enrolled and followed 1820 patients with ischemic or nonischemic cardiomyopathy, an ejection fraction of 30% or less, a QRS duration of 130 msec or more, and New York Heart Association class I or II symptoms. Patients were randomly assigned in a 3:2 ratio to receive CRT plus an implantable cardioverter– defibrillator (ICD) (1089 patients) or an ICD alone (731 patients). The primary end point was death from any cause or a nonfatal heart-failure event (whichever came first). Heartfailure events were diagnosed by physicians who were aware of the treatment assignments, but they were adjudicated by a committee that was unaware of assignments. Results During an average follow-up of 2.4 years, the primary end point occurred in 187 of 1089 patients in the CRT–ICD group (17.2%) and 185 of 731 patients in the ICD-only group (25.3%) (hazard ratio in the CRT–ICD group, 0.66; 95% confidence interval [CI], 0.52 to 0.84; P = 0.001). The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy. The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events, a finding that was evident primarily in a prespecified subgroup of patients with a QRS duration of 150 msec or more. CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction. There was no significant difference between the two groups in the overall risk of death, with a 3% annual mortality rate in each treatment group. Serious adverse events were infrequent in the two groups. Conclusions CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex. (ClinicalTrials.gov number, NCT ) N Engl J Med 2009; 361: Moss A. N Engl J Med 2009; 361:

10 MADIT-CRT: Subgroup Analysis
Cardiac-Resynchronization Therapy for the Prevention of Heart-Failure Events Arthur J. Moss, W. Jackson Hall, David S. Cannom, Helmut Klein, Mary W. Brown, James P. Daubert, N.A. Mark Estes III, Elyse Foster, Henry Greenberg, Steven L. Higgins, Marc A. Pfeffer, Scott D. Solomon, M.D., David Wilber, and Wojciech Zareba, for the MADIT-CRT Trial Investigators Background This trial was designed to determine whether cardiac-resynchronization therapy (CRT) with biventricular pacing would reduce the risk of death or heart-failure events in patients with mild cardiac symptoms, a reduced ejection fraction, and a wide QRS complex. Methods During a 4.5-year period, we enrolled and followed 1820 patients with ischemic or nonischemic cardiomyopathy, an ejection fraction of 30% or less, a QRS duration of 130 msec or more, and New York Heart Association class I or II symptoms. Patients were randomly assigned in a 3:2 ratio to receive CRT plus an implantable cardioverter– defibrillator (ICD) (1089 patients) or an ICD alone (731 patients). The primary end point was death from any cause or a nonfatal heart-failure event (whichever came first). Heartfailure events were diagnosed by physicians who were aware of the treatment assignments, but they were adjudicated by a committee that was unaware of assignments. Results During an average follow-up of 2.4 years, the primary end point occurred in 187 of 1089 patients in the CRT–ICD group (17.2%) and 185 of 731 patients in the ICD-only group (25.3%) (hazard ratio in the CRT–ICD group, 0.66; 95% confidence interval [CI], 0.52 to 0.84; P = 0.001). The benefit did not differ significantly between patients with ischemic cardiomyopathy and those with nonischemic cardiomyopathy. The superiority of CRT was driven by a 41% reduction in the risk of heart-failure events, a finding that was evident primarily in a prespecified subgroup of patients with a QRS duration of 150 msec or more. CRT was associated with a significant reduction in left ventricular volumes and improvement in the ejection fraction. There was no significant difference between the two groups in the overall risk of death, with a 3% annual mortality rate in each treatment group. Serious adverse events were infrequent in the two groups. Conclusions CRT combined with ICD decreased the risk of heart-failure events in relatively asymptomatic patients with a low ejection fraction and wide QRS complex. (ClinicalTrials.gov number, NCT ) N Engl J Med 2009; 361: Moss A. N Engl J Med 2009; 361:

11 1 month after randomization
RAFT Comparison between ICD and CRT-D in mild HF 34 centres: Canada (24), Europe (8), Australia (2) Enrolment n=1,798 Randomization Double-blinded Follow-up 40 months CRT-D NYHA Class II and III (till Feb. 2006, 20% of pts.) QRS 120 ms or 200 ms (paced) EF 30% n=904 Primary endpoint: Death from any cause or HF hospitalization 1:1 Cardiac-Resynchronization Therapy for Mild-to-Moderate Heart Failure Anthony S.L. Tang, George A. Wells, Mario Talajic, Malcolm O. Arnold, Robert Sheldon, Stuart Connolly, Stefan H. Hohnloser, Graham Nichol, David H. Birnie, John L. Sapp, Raymond Yee, Jeffrey S. Healey, and Jean L. Rouleau, for the Resynchronization–Defibrillation for Ambulatory Heart Failure Trial (RAFT) Investigators Background Cardiac-resynchronization therapy (CRT) benefits patients with left ventricular systolic dysfunction and a wide QRS complex. Most of these patients are candidates for an implantable cardioverter–defibrillator (ICD). We evaluated whether adding CRT to an ICD and optimal medical therapy might reduce mortality and morbidity among such patients. Methods We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more or a paced QRS duration of 200 msec or more to receive either an ICD alone or an ICD plus CRT. The primary outcome was death from any cause or hospitalization for heart failure. Results We followed 1798 patients for a mean of 40 months. The primary outcome occurred in 297 of 894 patients (33.2%) in the ICD–CRT group and 364 of 904 patients (40.3%) in the ICD group (hazard ratio in the ICD–CRT group, 0.75; 95% confidence interval [CI], 0.64 to 0.87; P<0.001). In the ICD–CRT group, 186 patients died, as compared with 236 in the ICD group (hazard ratio, 0.75; 95% CI, 0.62 to 0.91; P = 0.003), and 174 patients were hospitalized for heart failure, as compared with 236 in the ICD group (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). However, at 30 days after device implantation, adverse events had occurred in 124 patients in the ICD-CRT group, as compared with 58 in the ICD group (P<0.001). Conclusions Among patients with NYHA class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure. This improvement was accompanied by more adverse events. This article was published on November 14, 2010, at NEJM.org. ICD n=894 Follow up 1 month after randomization Follow up visits every 6 months Tang AS. N Engl J Med 2010 published online on November 14, 2010

12 CRT reduces HF/Mortality in mild HF
25% reduction in HF hospitalization or death NYHA II: 27% (p=0.001), NYHA III: 24% (p=0.04) Cardiac-Resynchronization Therapy for Mild-to-Moderate Heart Failure Anthony S.L. Tang, George A. Wells, Mario Talajic, Malcolm O. Arnold, Robert Sheldon, Stuart Connolly, Stefan H. Hohnloser, Graham Nichol, David H. Birnie, John L. Sapp, Raymond Yee, Jeffrey S. Healey, and Jean L. Rouleau, for the Resynchronization–Defibrillation for Ambulatory Heart Failure Trial (RAFT) Investigators Background Cardiac-resynchronization therapy (CRT) benefits patients with left ventricular systolic dysfunction and a wide QRS complex. Most of these patients are candidates for an implantable cardioverter–defibrillator (ICD). We evaluated whether adding CRT to an ICD and optimal medical therapy might reduce mortality and morbidity among such patients. Methods We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more or a paced QRS duration of 200 msec or more to receive either an ICD alone or an ICD plus CRT. The primary outcome was death from any cause or hospitalization for heart failure. Results We followed 1798 patients for a mean of 40 months. The primary outcome occurred in 297 of 894 patients (33.2%) in the ICD–CRT group and 364 of 904 patients (40.3%) in the ICD group (hazard ratio in the ICD–CRT group, 0.75; 95% confidence interval [CI], 0.64 to 0.87; P<0.001). In the ICD–CRT group, 186 patients died, as compared with 236 in the ICD group (hazard ratio, 0.75; 95% CI, 0.62 to 0.91; P = 0.003), and 174 patients were hospitalized for heart failure, as compared with 236 in the ICD group (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). However, at 30 days after device implantation, adverse events had occurred in 124 patients in the ICD-CRT group, as compared with 58 in the ICD group (P<0.001). Conclusions Among patients with NYHA class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure. This improvement was accompanied by more adverse events. This article was published on November 14, 2010, at NEJM.org. Tang AS. N Engl J Med 2010 published online on November 14, 2010

13 CRT reduces Mortality in mild HF
25% mortality reduction NYHA II: 29% (p=0.006), NYHA III: 21% (p=0.14) Cardiac-Resynchronization Therapy for Mild-to-Moderate Heart Failure Anthony S.L. Tang, George A. Wells, Mario Talajic, Malcolm O. Arnold, Robert Sheldon, Stuart Connolly, Stefan H. Hohnloser, Graham Nichol, David H. Birnie, John L. Sapp, Raymond Yee, Jeffrey S. Healey, and Jean L. Rouleau, for the Resynchronization–Defibrillation for Ambulatory Heart Failure Trial (RAFT) Investigators Background Cardiac-resynchronization therapy (CRT) benefits patients with left ventricular systolic dysfunction and a wide QRS complex. Most of these patients are candidates for an implantable cardioverter–defibrillator (ICD). We evaluated whether adding CRT to an ICD and optimal medical therapy might reduce mortality and morbidity among such patients. Methods We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more or a paced QRS duration of 200 msec or more to receive either an ICD alone or an ICD plus CRT. The primary outcome was death from any cause or hospitalization for heart failure. Results We followed 1798 patients for a mean of 40 months. The primary outcome occurred in 297 of 894 patients (33.2%) in the ICD–CRT group and 364 of 904 patients (40.3%) in the ICD group (hazard ratio in the ICD–CRT group, 0.75; 95% confidence interval [CI], 0.64 to 0.87; P<0.001). In the ICD–CRT group, 186 patients died, as compared with 236 in the ICD group (hazard ratio, 0.75; 95% CI, 0.62 to 0.91; P = 0.003), and 174 patients were hospitalized for heart failure, as compared with 236 in the ICD group (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). However, at 30 days after device implantation, adverse events had occurred in 124 patients in the ICD-CRT group, as compared with 58 in the ICD group (P<0.001). Conclusions Among patients with NYHA class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure. This improvement was accompanied by more adverse events. This article was published on November 14, 2010, at NEJM.org. Tang AS. N Engl J Med 2010 published online on November 14, 2010

14 Results for NYHA II and III
Cardiac-Resynchronization Therapy for Mild-to-Moderate Heart Failure Anthony S.L. Tang, George A. Wells, Mario Talajic, Malcolm O. Arnold, Robert Sheldon, Stuart Connolly, Stefan H. Hohnloser, Graham Nichol, David H. Birnie, John L. Sapp, Raymond Yee, Jeffrey S. Healey, and Jean L. Rouleau, for the Resynchronization–Defibrillation for Ambulatory Heart Failure Trial (RAFT) Investigators Background Cardiac-resynchronization therapy (CRT) benefits patients with left ventricular systolic dysfunction and a wide QRS complex. Most of these patients are candidates for an implantable cardioverter–defibrillator (ICD). We evaluated whether adding CRT to an ICD and optimal medical therapy might reduce mortality and morbidity among such patients. Methods We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more or a paced QRS duration of 200 msec or more to receive either an ICD alone or an ICD plus CRT. The primary outcome was death from any cause or hospitalization for heart failure. Results We followed 1798 patients for a mean of 40 months. The primary outcome occurred in 297 of 894 patients (33.2%) in the ICD–CRT group and 364 of 904 patients (40.3%) in the ICD group (hazard ratio in the ICD–CRT group, 0.75; 95% confidence interval [CI], 0.64 to 0.87; P<0.001). In the ICD–CRT group, 186 patients died, as compared with 236 in the ICD group (hazard ratio, 0.75; 95% CI, 0.62 to 0.91; P = 0.003), and 174 patients were hospitalized for heart failure, as compared with 236 in the ICD group (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). However, at 30 days after device implantation, adverse events had occurred in 124 patients in the ICD-CRT group, as compared with 58 in the ICD group (P<0.001). Conclusions Among patients with NYHA class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure. This improvement was accompanied by more adverse events. This article was published on November 14, 2010, at NEJM.org. Tang AS. N Engl J Med 2010 published online on November 14, 2010

15 RAFT: Outcomes in Pts. with Chronic AF Analysis after 6 months by % Vpacing in first 6 months
P value Death or HF hospitalization 26 (41%) 14 (42%) 0.87 ( ) 0.68 All-cause mortality 21 (31%) 12 (34%) 0.90 ( ) 0.76 CV death 16 (23%) 4 (11%) 0.37 ( ) 0.066 CV hospitalization 21 (35%) 12 (40%) 1.20 ( ) 0.62 Hohnloser S. Presented during the ESC congress on August 31, 2011

16 RAFT: Outcomes in Pts. with Chronic AF 229 Patients with AF at baseline
ICD only (n=115) ICD/CRT (n=114) HR (95% CI) P value Death or HF hospitalization 49 (43%) 55 (48%) 0.96 ( ) 0.82 All-cause mortality 35 (30%) 42 (37%) 1.04 ( ) 0.88 CV death 23 (20%) 26 (23%) 0.97 ( ) 0.91 HF hospitalization 32 (28%) 22 (19%) 0.58 0.052 CV hospitalization 51 (44%) 54 (47%) ( ) 0.84 Hohnloser S. Presented during the ESC congress on August 31, 2011

17 CRT and Mortality: Meta-analysis
Meta-analysis of 12 CRT studies with 7,538 pts. Interpretation: CRT reduces mortality in HF pts. Cardiac resynchronization therapy: a meta-analysis of randomized controlled trials George Wells PhD, Ratika Parkash MD MSc, Jeffrey S. Healey MD MSc, Mario Talajic MD, J. Malcolm Arnold MD, Shannon Sullivan MSc, Joan Peterson BA, Elizabeth Yetisir MSc, Patricia Theoret-Patrick BScRN, Marilynn Luce BScRN, Anthony S.L. Tang MD Background: Studies of cardiac resynchronization therapy in addition to an implantable cardioverter defibrillator in patients with mild to moderate congestive heart failure had not been shown to reduce mortality until the re cent RAFT trial (Resynchronization/ Defibrillation for Ambulatory Heart Failure Trial). We performed a meta-analysis including the RAFT trial to de termine the effect of cardiac resynchronization therapy with or without an im plant able defibrillator on mortality. Methods: We searched electronic databases and other sources for reports of randomized trials using a parallel or crossover design. We included studies involving patients with heart failure receiving optimal medical therapy that compared cardiac resynchronization therapy with optimal medical therapy alone, or cardiac resynchronization therapy plus an implantable defibrillator with a standard implantable defibrillator. The primary outcome was mortality. The optimum information size was considered to assess the minimum amount of in formation required in the literature to reach reliable conclusions about cardiac resynchronization therapy. Results: Of 3071 reports identified, 12 studies (n = 7538) were included in our meta- analysis. Compared with optimal medical therapy alone, cardiac resynchronization therapy plus optimal medical therapy significantly reduced mortality (relative risk [RR] 0.73, 95% confidence interval [CI] 0.62–0.85). Compared with an implantable defibrillator alone, cardiac resynchronization therapy plus an implant - able defibrillator significantly reduced mortality (RR 0.83, 95% CI 0.72–0.96). This last finding remained significant among patients with New York Heart Association (NYHA) class I or II disease (RR 0.80, 95% CI 0.67–0.96) but not among those with class III or IV disease (RR 0.84, 95% CI 0.69–1.07). Analysis of the optimum information size showed that the sequential monitoring boundary was crossed, which suggests no need for further clinical trials. Interpretation: The cumulative evidence is now conclusive that the addition of cardiac resynchronization to optimal medical therapy or defibrillator therapy significantly reduces mortality among patients with heart failure. Wells G. Canadian Medical Association Journal 2011, advance access published on January 31, 2011

18 CRT in mild HF: Meta-analysis
Meta-analysis of 5 studies of CRT in mild HF including 4,317 pts. CRT decreases all-cause mortality, reduces HF hospitalizations and improves LVEF Cardiac Resynchronization Therapy in Patients With Minimal Heart Failure: A Systematic Review and Meta-Analysis Selcuk Adabag, Henri Roukoz, Inder S. Anand, Arthur J. Moss Objectives The purpose of this study was to perform a systematic review and meta-analysis of prospective randomized clinical trials of cardiac resynchronization therapy (CRT) versus implantable cardioverter-defibrillator (ICD) in patients with reduced ejection fraction (EF), prolonged QRS interval, and New York Heart Association (NYHA) functional class I to II heart failure (HF). Background In patients with advanced HF, CRT improves left ventricular (LV) function and reduces mortality and hospitalizations. Recent data suggest that patients with milder HF also benefit from CRT. Methods A meta-analysis of 5 clinical trials including 4,317 patients with NYHA functional class I/II HF was performed. Results Average age of patients was 65 years, and 80% were male. Frequency of all-cause mortality for CRT versus ICD was 8% versus 11.5% (risk ratio [RR]: 0.81; 95% confidence interval [CI]: 0.65 to 0.99, p = 0.04); for HF hospitalization, it was 11.6% versus 18.2% (RR: 0.68; 95% CI: 0.59 to 0.79, p < 0.001). Patients assigned to CRT had a significantly greater improvement in LVEF (5.9% vs. 2.2%, p < 0.001) and LV volume than ICD patients. Among mildly symptomatic (NYHA functional class II) patients, CRT was associated with significantly lower mortality and HF hospitalization (RR: 0.73; 95% CI: 0.64 to 0.83), p < 0.001). In asymptomatic (NYHA functional class I) patients, HF hospitalization risk was lower (RR: 0.57; 95% CI: 0.34 to 0.97, p = 0.04) with CRT; however, there was no difference in mortality. Twelve asymptomatic HF patients needed to be treated with CRT to prevent 1 hospitalization. Conclusions Cardiac resynchronization therapy decreases all-cause mortality, reduces HF hospitalizations, and improves LVEF in NYHA functional class I/II HF patients. Although there was a reduction in HF hospitalization with CRT for asymptomatic (NYHA functional class I) patients, risks versus benefits have to be carefully considered in this subgroup. J Am Coll Cardiol 2011;58:935–41 Adabag S. J Am Coll Cardiol 2011; 58: 935–41

19 European CRT Survey The European cardiac resynchronization therapy survey Kenneth Dickstein, Nigussie Bogale, Silvia Priori, Angelo Auricchio, John G. Cleland, Anselm Gitt, Tobias Limbourg, Cecilia Linde, Dirk J. van Veldhuisen, and Josep Brugada on behalf of the Scientific Committee and National Coordinators Aims The European cardiac resynchronization therapy (CRT) survey is a joint initiative taken by the Heart Failure Association and the European Heart Rhythm Association of the European Society of Cardiology. The primary aim of this survey is to describe current European practice associated with CRT implantations. Methods and results A total of 140 centres from 13 European countries contributed data from consecutive patients successfully implanted with a CRT device with or without an ICD between November 2008 and June The total number of patients enrolled was The median age of the patients was 70 years (IQR 62–76) and 31% were ≥75 years. It was found that 78% were in NYHA functional class III or IV and 22% in I or II. The mean ejection fraction was 27%±8 and the mean QRS duration 157 ms±32. The QRS duration was <120 ms in 9%. Atrial fibrillation was reported in 23%. It was found that 26% of patients had a previously implanted permanent pacemaker or ICD; 76% of procedures were performed by an electrophysiologist; 82% had an elective admission for implantation and the median duration of hospitalization was 3 days (IQR 2–7); and 73% received a CRT-D device which was more often implanted in men, younger patients, and with ischaemic aetiology. The mean QRS duration was reduced to 133 ms±27 (P < ) at discharge. Peri-procedural complication rates were comparable to the rates reported in randomized trials. Conclusion This CRT survey provides important information describing current European practice with regard to patient demographics, selection criteria, procedural routines, and status at discharge. These data should be useful for benchmarking individual patient management and national practice against wider experience. Dickstein K. European Heart Journal 2009 advance access published August 31, 2009

20 CRT in Mild Heart Failure
2010 Focused Update of ESC guidelines on device therapy in heart failure Keypoints: - Two recent, randomized, prospective, multicentre trials in mild HF (MADIT-CRT and REVERSE) demonstrate reduced morbidity. - 18% of patients in REVERSE and 15% of patients in MADIT-CRT were in NYHA I class at baseline although most of these patients had been previously symptomatic. - Improvement primarily seen in patients with QRS ≥150 ms and/or typical LBBB. - In MADIT-CRT, women with LBBB demonstrated a particularly favourable response. - Survival advantage not established. - In MADIT-CRT the extent of reverse remodelling was concordant with and predictive of improvement in clinical outcomes. Dickstein K. Europace 2010; 12: 1526–1536

21 Cost Effectiveness of CRT in Mild HF
Health care economics substudy REVERSE (262 pts.) CRT is cost-effective for mild HF: Incremental cost-effectiveness ratio (ICER): €14,278 per QALY CRT becomes cost-effective after 4.5 years Cost-effectiveness of cardiac resynchronization therapy in patients with asymptomatic to mild heart failure: insights from the European cohort of the REVERSE (Resynchronization Reverses remodeling in Systolic Left Ventricular Dysfunction) Cecilia Linde, Stuart Mealing, Neil Hawkins, James Eaton, Ben Brown, and Jean-Claude Daubert, on behalf of the REVERSE study group Aims To assess the cost-effectiveness of cardiac resynchronization therapy (CRT) compared with optimal medical therapy in patients with New York Heart Association (NYHA) II heart failure (HF) or NYHA I with previous HF symptoms. Methods and results A proportion in state model with Monte Carlo simulation was developed to assess the costs, life years and quality adjusted life year (QALYs) associated with CRT-ON and -OFF over a 10 year time period. Data from 262 patients in the European cohort of the REVERSE clinical trial (QRS ≥ 120 ms, left ventricular ejection fraction ≤ 40%, CRT-ON, n = 180, CRT-OFF, n = 82) were used to model all-cause mortality, change in NYHA class and resource use. EQ-5D preference weights were taken from a previous cost-effectiveness model of CRT and unit costs from national UK databases. Costs and benefits were discounted at 3.5% p.a. Extensive deterministic and probabilistic sensitivity analyses were performed. Compared with CRT-OFF, 0.94 life years or 0.80 QALYs were gained in the CRT ON group at an additional cost of € , yielding an incremental cost-effectiveness ratio of € per quality-adjusted life year (QALY) gained. At a threshold of € (£30 000) per QALY gained, the probability that CRT is cost-effective is 79.6%. Cardiac resynchronization therapy becomes cost effective after 4.5 years. Cardiac resynchronization therapy needs only to demonstrate a modest impact on all cause mortality (hazard ratio = 0.82) in order to demonstrate cost-effectiveness. The results are robust to changes in all other parameters. Conclusion Cardiac resynchronization therapy is a cost-effective intervention for patients with mildly symptomatic HF and for asymptomatic patients with left ventricular dysfunction and previous HF symptoms. European Heart Journal Advance Access published November 25, 2010 Linde C. Eur Heart J advance access published on November 25, 2010

22 Doporučení ČKS pro diagnostiku a léčbu srdečního selhání

23 Současné indikace SRL I
Základní rytmus NYHA klasifikace Indikační kritéria Indikační třída Úroveň důkazů Cíle terapie Doporučené přístroje SR III-IV EF LK < 0.35, QRS > 120 ms, optimální medikamentózní léčba srdečního selhání. Pacienti třídy NYHA IV by měli být schopni chodit a předpokládané přežití by mělo být > 6 měsíců I A Snížení morbidity a mortality Použití BiV-KS nebo BiV-ICD II (I) EF LK < 0.35, QRS > 150 ms !, optimální medikamentózní léčba srdečního selhání. Pro třídu NYHA I není v současné době dostatek informací. Snížení morbidity, mortality a progrese základního onemocnění Použití preferenčně BiV-ICD

24 Současné indikace SRL II
Základní rytmus NYHA klasifikace Indikační kritéria Indikační třída Úroveň důkazů Cíle terapie Doporučené přístroje FS III EF LK < 0.35, QRS > 130 ms, dependence na KS po RFA AVJ / FS s pomalou komorovou odpovědí a frekventní stimulací IIa B /C Snížení morbidity Použití BiV-KS nebo BiV-ICD Současná indikace trvalé kardiostimulace třídy I a srdeční selhání III, IV II EF LK < 0.35, QRS > 120 ms, optimální medikamentózní léčba srdečního selhání EF LK < 0.35, QRS < 120 ms, optimální medikamentózní léčba srdečního selhání EF LK <0.35, QRS < 120 ms, optimální medikamentózní léčba srdečního selhání I IIb B C

25 Závěr SRL je etablovaná léčba u nemocných se srdečním selháním a komorovou dyssynchronií jasný posun z pozdních do časných indikací SRL  prevence pokračující remodelace NYHA II: vždy BiV ICD NYHA III-IV: zvážit BiV ICD nebo BiV KS trvající kontroverze – výběr pacientů role echokardiografie selektivní poloha LK (PK) EL management komplikací budoucnost: leadless pacing buněčné intervence

26 Pacientka s PCI anterolaterální žíly a následnou implantací LK EL

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